Adenosine receptors are ubiquitous and appear to be involved in the biochemical activity of many cell types. Among the adenosine receptors, those which activate adenylate cyclase are the most abundant and have attracted the widest attention. These receptors seem to mediate numerous important physiological activities such as dilation of blood vessels in the heart and modulation of neurotransmission in the central nervous system and the periphery. The adenosine receptors that mediate these activities can be studied by biochemical tools, since the same receptors are found in biological systems more amenable to biochemical manipulations than the ones mentioned above. In this project we are synthesizing new specific and high affinity ligands for: (a) characterization of adenosine receptors by binding experiments; (b) developing covalent affinity labels for the adenosine receptor; (c) developing matrix bound ligands which can be used to purify the adenosine receptor; and (d) develop fluorescent ligands which can be used to identify and map adenosine receptors in intact tissues. The development of these chemical probes will also allow the investigation of the mode of interaction between the adenosine receptor and the enzyme adenylate cyclase, using a similar approach to that we developed for the beta-adrenergic dependent adenylate cyclase. Last but not least, the interrelationship between beta-receptors and adenosine receptors, which occurs in some tissues simultaneously, will be explored in detail.